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Cocaine induces differential circular RNA expression in striatum

机译:可卡因在纹状体中诱导差异环状RNA表达

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摘要

Circular RNA (circRNA), a novel type of endogenous non-coding RNA, plays natural miRNA sponge effect that represses the activities of corresponding miRNAs through binding with them, thus modulating transcriptional expression of genes. Recent studies indicate that circRNAs are significantly enriched in the brain and some of them are derived from synaptic protein-coding genes. In addition, miRNAs are involved in synaptic plasticity, memory formation, and cocaine addiction. However, the role of circRNAs in cocaine reward is unclear. This study aimed to investigate the expression profile of striatal circRNAs in the mice after cocaine self-administration. By using circRNA microarray analysis, we observed that 90 striatal circRNAs were differentially expressed in cocaine self-administering mice, of which 18 circRNAs were up-regulated and 72 down-regulated. Six circRNAs were selected randomly for validation by using quantitative reverse transcription-PCR, and their expression levels showed consistency with microarray analysis. We backward predicted the circRNAs and their binding sites of miRNAs associated with neuroplasticity. In functional validation test, mmu_circRNA_002381 may modulate the transcription of certain genes associated with neuroplasticity, such as limk1 and bdnf. Taken together, circRNAs may participate in cocaine behavioral effect via interacting with miRNAs. Our findings reveal a potential role of circRNAs in cocaine effect.
机译:环状RNA(circRNA)是一种新型的内源性非编码RNA,具有天然的miRNA海绵效应,可通过与相应的miRNA结合来抑制相应miRNA的活性,从而调节基因的转录表达。最近的研究表明,circRNA在大脑中显着富集,其中一些来源于突触蛋白编码基因。另外,miRNA参与突触可塑性,记忆形成和可卡因成瘾。但是,尚不清楚circRNA在可卡因奖励中的作用。这项研究旨在调查可卡因自我给药后纹状体circRNA在小鼠中的表达情况。通过使用circRNA芯片分析,我们观察到90纹状体circRNA在可卡因自给药小鼠中差异表达,其中18枚circRNA上调而72枚下调。通过定量逆转录-PCR随机选择了六个circRNA进行验证,其表达水平与微阵列分析一致。我们向后预测了circRNA及其与神经可塑性相关的miRNA的结合位点。在功能验证测试中,mmu_circRNA_002381可以调节某些与神经可塑性相关的基因的转录,例如limk1和bdnf。总之,circRNA可能通过与miRNA相互作用而参与可卡因的行为效应。我们的发现揭示了circRNA在可卡因效应中的潜在作用。

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